Synthesis of tetrahydrofurans by asymmetric mercuriocyclization

Abstract

Electrophilic cyclization of unsaturated carboxylic acids, alcohols and amines is important biomimetic process in the synthesis of heterocyclic intermediate and the functionalization of double bonds. Also, it has been intended for asymmetric modification. Some of successful reagent-controlled electrophilic cyclization reactions have been developed involving chiral synthetic iodoreagents, mercuric salts, and selenium reagents as electrophiles. Among various kinds of electrophilic cyclization reactions, iodoetherification was examined for its asymmetric variants because it gave tetrahydrofurans or tetrahydropyrans which were useful synthetic moieties in organic synthesis. The standard substrate 81c was designed to undergo 5-exo iodoetherification giving a chiral tetrahydrofuran-containing compound and used for comparing the level of enantioselectivity in all asymmetric electrophile-promoted cyclization reaction performed. First, chiral iodoreagents 73a-d modeled on N-iodosuccinimide (NCS) were synthesized but failed to promote iodoetherification. Second, a variety of chiral Lewis bases were synthesized and employed to activate iodoreagents at low temperature where no spontaneous iodoetherification reaction occurred without Lewis bases. One-to-one complexes of chiral Lewis bases 85-95 and NIS or $I_2$ were generated in situ and then substrate 81c was added, which gave low enantioselectivity. Among several Lewis base, bisoxazolines 79a and 80 showed the best result (20 - 30% ee). Asymmetric mercurioetherification was tried with the complexes of bisoxazolines and $Hg(CF_3CO_2)_2$. Bisoxazolines with $C_4-phenyl$ group promoted the desired mercurioetherification and gave higher enantioselectivity than that of iodoetherification. In the case of bisoxazoline 80, the reaction rate was very fast and gave 63% ee in dichloromethane. When diethyl ether or potassium carbonate was added, the enantioselectivity increased to 70% ee. Many $C_4-phenyl$ bearing...